Implementation of French Recommendations for the Prevention and the Treatment of Hospital-acquired Pneumonia: A Cluster-randomized Trial.

BACKGROUND: We determined whether an audit on the adherence to guidelines for hospital-acquired pneumonia (HAP) can improve the outcomes of patients in intensive care units (ICUs). METHODS: This study was conducted at 35 ICUs in 30 hospitals. We included consecutive, adult patients hospitalized in ICUs for 3 days or more. After a 3-month baseline period followed by the dissemination of recommendations, an audit on the compliance to recommendations (audit period) was followed by a 3-month cluster-randomized trial. We randomly assigned ICUs to either receive audit and feedback (intervention group) or participate in a national registry (control group). The primary outcome was the duration of ICU stay. RESULTS: Among 1856 patients enrolled, 602, 669, and 585 were recruited in the baseline, audit, and intervention periods, respectively. The composite measures of compliance were 47% (interquartile range [IQR], 38-56%) in the intervention group and 42% (IQR, 25-53%) in the control group (P = .001). As compared to the baseline period, the ICU lengths of stay were reduced by 3.2 days in the intervention period (P = .07) and by 2.8 days in the control period (P = .02). The durations of ICU stay were 7 days (IQR, 5-14 days) in the control group and 9 days (IQR, 5-20 days) in the intervention group (P = .10). After adjustment for unbalanced baseline characteristics, the hazard ratio for being discharged alive from the ICU in the control group was 1.17 (95% confidence interval, .69-2.01; P = .10). CONCLUSIONS: The publication of French guidelines for HAP was associated with a reduction of the ICU length of stay. However, the realization of an audit to improve their application did not further improve outcomes. CLINICAL TRIALS REGISTRATION: NCT03348579.

Platelet activation and partial desensitization are associated with viral xenophagy in patients with severe COVID-19.

Mild thrombocytopenia, changes in platelet gene expression, enhanced platelet functionality, and presence of platelet-rich thrombi in the lung have been associated with thromboinflammatory complications of patients with COVID-19. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gets internalized by platelets and directly alters their behavior and function in infected patients remains elusive. Here, we investigated platelet parameters and the presence of viral material in platelets from a prospective cohort of 29 patients with severe COVID-19 admitted to an intensive care unit. A combination of specific assays, tandem mass spectrometry, and flow cytometry indicated high levels of protein and lipid platelet activation markers in the plasma from patients with severe COVID-19 associated with an increase of proinflammatory cytokines and leukocyte-platelets interactions. Platelets were partly desensitized, as shown by a significant reduction of αIIbß3 activation and granule secretion in response to stimulation and a decrease of surface GPVI, whereas plasma from patients with severe COVID-19 potentiated washed healthy platelet aggregation response. Transmission electron microscopy indicated the presence of SARS-CoV-2 particles in a significant fraction of platelets as confirmed by immunogold labeling and immunofluorescence imaging of Spike and nucleocapsid proteins. Compared with platelets from healthy donors or patients with bacterial sepsis, platelets from patients with severe COVID-19 exhibited enlarged intracellular vesicles and autophagolysosomes. They had large LC3-positive structures and increased levels of LC3II with a co-localization of LC3 and Spike, suggesting that platelets can digest SARS-CoV-2 material by xenophagy in critically ill patients. Altogether, these data show that during severe COVID-19, platelets get activated, become partly desensitized, and develop a selective autophagy response.

Thromboembolic events and Covid-19.

The novel Corona virus infection (Covid-19) first identified in China in December 2019 has rapidly progressed in pandemic leading to significant mortality and unprecedented challenge for healthcare systems. Although the clinical spectrum of Covid-19 is variable, acute respiratory failure and systemic coagulopathy are common in severe Covid-19 patients. Lung is an important target of the SARS-CoV-2 virus causing eventually acute respiratory distress syndrome associated to a thromboinflammatory state. The cytokinic storm, thromboinflammation and pulmonary tropism are the bedrock of tissue lesions responsible for acute respiratory failure and for prolonged infection that may lead to multiple organ failure and death. The thrombogenicity of this infectious disease is illustrated by the high frequency of thromboembolic events observed even in Covid-19 patients treated with anticoagulation. Increased D-Dimers, a biomarker reflecting activation of hemostasis and fibrinolysis, and low platelet count (thrombocytopenia) are associated with higher mortality in Covid-19 patients. In this review, we will summarize our current knowledge on the thromboembolic manifestations, the disturbed hemostatic parameters, and the thromboinflammatory conditions associated to Covid-19 and we will discuss the modalities of anticoagulant treatment or other potential antithrombotic options.

Early Massive Pulmonary Embolism After Total Hip Arthroplasty in a Patient With Behcet Disease: A Case Report.

Venous complications in Behcet disease (BD) affect nearly 40% of patients. We describe a woman with BD who presented with a massive bilateral pulmonary embolism 30 hours after total hip arthroplasty. The patient underwent surgical thrombectomy and venoarterial extracorporeal membrane oxygenation. Methotrexate was withheld 15 days before surgery and restarted on postoperative day 2. Immunosuppressive therapy, such as methotrexate, appears to be the most effective prophylactic treatment for venous thrombosis in patients with BD, whereas prophylaxis with low-molecular-weight heparin may be ineffective, as was the situation in our patient. Therefore, continuation of methotrexate perioperatively should be considered in patients with BD. Systematically performing preoperative deep vein thrombosis screening should be also considered. The patient also had diabetes mellitus treated with metformin and sitagliptin preoperatively.